The continued high rates of preterm delivery in the U.S, particularly among African-American women and poor women, suggests that new paradigms are needed to study this complex public health problem. We propose a placental abnormality-based model for studying PTD subtypes which assesses three major pathways to PTD, one predominantly characterized by placental and fetal membrane infection/inflammation, the second by placental and decidual vascular abnormalities, and the third by premature increases in the production of placental CRH without histopathologic abnormalities. Within each pathway we trace early biologic indicators of underlying pathology, and their psychosocial and behavioral antecedents - many of which are potential targets for primary and secondary prevention strategies. To test this model we have assembled an unusually diverse, community-based, prospective cohort of 1,403 pregnant women enrolled from 52 prenatal clinics located within 5 Michigan cities. The cohort study, currently funded by NICHD, has a goal of enrolling 2,903 women by the end of the proposed continuation. The cohort is unique in that it includes collection of multiple biologic samples (hair, urine, blood, vaginal fluid), obtains in-depth maternal interviews, 24 hour ambulatory blood pressure measures, salivary cortisol and urinary catecholamine levels (collected AM and PM for 3 consecutive days), a detailed gross and histological examination of delivered placentas, medical record abstraction, assessment of DNA polymorphisms as effect modifiers, and linkage to census data for ecological level social variables. Most importantly, biologic samples are collected in the second trimester, well before onset of labor and earlier than most published prospective studies of PTD. Research into the origins of prematurity has been largely undertaken from either a psychosocial or a biochemical perspective. This comprehensive study aims to unify both approaches into a coherent causal framework based on a foundation of specific placental findings that we hypothesize underlie several routes to PTD.